The long-range objective of this research is to determine the number, function and regulation of the I (immune response) region genes of the H-2 gene complex. The discovery of a set of lymphocyte alloantigenic specificities controlled by I region genes and designated the Ia antigens promises to be of great value as a tool for the elucidation of the various I region traits and thereby of some fundamental mechanisms of immune response. The immediate objective of the proposed research is to better define and characterize these Ia antigens. The principal aims are: 1) to identify the multiple Ia specificities controlled by each H-2 haplotype and to define each by a "monospecific" antiserum; 2) to define and map the genes controlling the Ia antigens by analysis of H-2 recombinants and mutants; 3) to define the expression of individual Ia specificities on normal T and B lymphocytes and lymphoid tumor cells; 4) to determine the number and chemical properties of the various distinct Ia antigen molecules.